Background/Objectives: The use of linezolid in drug-resistant tuberculosis has shown good effectiveness but has a high risk of adverse drug reactions (ADRs). Linezolid-related ADRs have been widely reported and may affect their therapeutic effect. This systematic review aimed to describe linezolid-related ADRs in drug-resistant tuberculosis. Methods: This literature review was conducted on PubMed, Scopus, ProQuest, and Sage without year limitation, up to June 2023. Study quality was assessed using the JBI checklist to evaluate method quality and risk of bias in the included articles. Inclusion criteria included studies assessing linezolid-correlated ADRs in drug-resistant tuberculosis patients with individual regimens, having access to the full text, and using the English or Indonesian language. Potential reporting bias was minimized by comprehensive database search and duplicate screening. Results: Initially, we identified 650 potential studies. Upon further assessment for relevance and eligibility, seven articles were selected for analysis. From seven articles, it was shown that all articles were reporting about linezolid-correlated ADRs. The three main ADRs are hematologic toxicity, peripheral neuropathy, and optic neuritis. In addition, gastrointestinal disorder and hyperlactatemia are reported as ADRs too. Varied doses of linezolid were used in the seven articles; they range from 300 mg to 1200 mg, with 600 mg/twice daily and 1200 mg/day being dominant. Conclusions: Linezolid-associated ADRs are dose- and duration-dependent. Hematological toxicity most commonly occurs at the beginning of treatment, while peripheral neuropathy and optic neuritis appear after long-term use. Therefore, intensive monitoring and therapeutic drug monitoring are essential to ensure the safety of linezolid therapy.

Context: Drug-resistant tuberculosis (DR-TB) remains a major public health challenge in Indonesia. Treatment outcomes are often compromised by adverse drug reactions (ADRs), particularly those related to prolonged linezolid use. Aims: To compare the incidence and temporal patterns of hematological and neurological ADRs between linezolid- and non-linezolid–based regimens in patients with DR-TB. Methods: A retrospective cohort study was conducted involving 295 DR-TB patients, including 278 receiving linezolid-based regimens and 17 receiving non-linezolid regimens. ADRs were identified from medical records, including patient-reported symptoms, clinical assessments, and laboratory data. Results: ADRs were more frequent in the linezolid group than in the non-linezolid group (268/278 vs 13/17). Anemia was the most common ADR among linezolid-treated patients (92.1%) and was significantly associated with linezolid use (aOR 8.15; 95%CI 2.28–23.50; p<0.001). Peripheral neuropathy occurred in 63.7% of patients and was also significantly associated with linezolid exposure (aOR 4.21; 95%CI 1.44–12.28; p = 0.005). Optic neuritis was less frequent (18.7%) and was not significantly associated with linezolid use. Anemia typically occurred within the first 1–5 months of treatment, whereas peripheral neuropathy and optic neuritis were associated with longer treatment duration. Distinct temporal patterns of ADRs onset were observed (Gray’s test, p<0.001). Conclusions: Linezolid-containing regimens were associated with a high burden of clinically significant ADRs in DR-TB treatment. Early-onset anemia and duration-dependent neurotoxicity highlight the importance of routine laboratory monitoring and structured neurological and ophthalmological surveillance during prolonged therapy.